Umemura K, Kikuchi S, Suzuki Y, Nakashima M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Jpn J Pharmacol. 1998 Oct;78(2):161-7. doi: 10.1254/jjp.78.161.
Tranilast, N-(3,4-dimethoxycinnamoyl) anthranilic acid, a widely used antiallergy drug in Japan, has been shown to inhibit transforming growth factor-beta1 release from fibroblasts and reduce collagen synthesis in keloid cells. In the present study, we have investigated the effect of this drug on cardiac hypertrophy in spontaneously hypertensive rats (SHR), with a focus on the cardiac collagen matrix, which is associated with myocardial stiffness. Twenty-four-week-old SHRs and Wistar Kyoto rats (WKYs) were administered tranilast (300 mg/kg) orally once a day for 4 weeks. This treatment significantly suppressed increases in left ventricular collagen concentration (P < 0.05) and the left ventricular weight/body weights ratios (P < 0.05) in SHRs, and tranilast was ineffective on collagen concentration and ventricular weight/body weights ratios in WKYs. Tranilast did not affect systolic or diastolic blood pressure, end-diastolic left ventricular pressure and heart rate in both SHRs and WKYs, and the agent did not change positive dp/dt or cardiac output in SHRs. The pressure-volume relationship curve was shifted to the left by the drug; the slope (k) of the logarithm of the pressure-volume relationship curve was significantly increased (P < 0.05) in SHRs. It is concluded that the suppression of increases in cardiac collagen and left ventricular mass by tranilast results in a corresponding prevention of cardiac stiffness as studied in the SHR.
曲尼司特，N-(3,4-二甲氧基肉桂酰)邻氨基苯甲酸，在日本是一种广泛使用的抗过敏药物，已被证明可抑制成纤维细胞释放转化生长因子-β1，并减少瘢痕疙瘩细胞中的胶原蛋白合成。在本研究中，我们研究了该药物对自发性高血压大鼠(SHR)心脏肥大的影响，重点关注与心肌僵硬度相关的心脏胶原基质。24周龄的SHR和Wistar Kyoto大鼠(WKY)每天口服一次曲尼司特(300 mg/kg)，持续4周。这种治疗显著抑制了SHR左心室胶原浓度的增加(P < 0.05)和左心室重量/体重比的增加(P < 0.05)，而曲尼司特对WKY的胶原浓度和心室重量/体重比无效。曲尼司特对SHR和WKY的收缩压或舒张压、舒张末期左心室压力和心率均无影响，且该药物对SHR的dp/dt正值或心输出量也无改变。药物使压力-容积关系曲线向左移动；SHR中压力-容积关系曲线对数的斜率(k)显著增加(P < 0.05)。结论是，曲尼司特抑制心脏胶原和左心室质量的增加，相应地预防了SHR中研究的心脏僵硬度。
